The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study.
Jacobi H., Bauer P., Giunti P., Labrum R., Sweeney MG., Charles P., Dürr A., Marelli C., Globas C., Linnemann C., Schöls L., Rakowicz M., Rola R., Zdzienicka E., Schmitz-Hübsch T., Fancellu R., Mariotti C., Tomasello C., Baliko L., Melegh B., Filla A., Rinaldi C., van de Warrenburg BP., Verstappen CCP., Szymanski S., Berciano J., Infante J., Timmann D., Boesch S., Hering S., Depondt C., Pandolfo M., Kang J-S., Ratzka S., Schulz J., Tezenas du Montcel S., Klockgether T.
OBJECTIVE: To obtain quantitative data on the progression of the most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated the EUROSCA natural history study, a multicentric longitudinal cohort study of 526 patients with SCA1, SCA2, SCA3, or SCA6. We report the results of the 1- and 2-year follow-up visits. METHODS: As the primary outcome measure we used the Scale for the Assessment and Rating of Ataxia (SARA, 0-40), and as a secondary measure the Inventory of Non-Ataxia Symptoms (INAS, 0-16) count. RESULTS: The annual increase of the SARA score was greatest in SCA1 (2.18 ± 0.17, mean ± SE) followed by SCA3 (1.61 ± 0.12) and SCA2 (1.40 ± 0.11). SARA progression in SCA6 was slowest and nonlinear (first year: 0.35 ± 0.34, second year: 1.44 ± 0.34). Analysis of the INAS count yielded similar results. Larger expanded repeats and earlier age at onset were associated with faster SARA progression in SCA1 and SCA2. In SCA1, repeat length of the expanded allele had a similar effect on INAS progression. In SCA3, SARA progression was influenced by the disease duration at inclusion, and INAS progression was faster in females. CONCLUSIONS: Our study gives a comprehensive quantitative account of disease progression in SCA1, SCA2, SCA3, and SCA6 and identifies factors that specifically affect disease progression.